Michael J. Lush

Bio: Michael J. Lush is an academic researcher from University College London. The author has contributed to research in topics: Medicine & Breast cancer. The author has an hindex of 10, co-authored 10 publications receiving 2834 citations.

Gene map of the extended human MHC

Abstract: The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in adaptive and innate immunity. Decades of biomedical research have revealed many MHC genes that are duplicated, polymorphic and associated with more diseases than any other region of the human genome. The recent completion of several large-scale studies offers the opportunity to assimilate the latest data into an integrated gene map of the extended human MHC. Here, we present this map and review its content in relation to paralogy, polymorphism, immune function and disease.

The HUGO Gene Nomenclature Committee (HGNC)

Abstract: The need for standard nomenclature in human genetics was recognised as early as the 1960s, and in 1979 full guidelines for human gene nomenclature were presented at the Edinburgh Human Genome Meeting (HGM) and subsequently published (Shows et al. 1979). The current Chair of the Human Gene Nomenclature Committee, Sue Povey, was elected at the HGM meeting in Heidelberg in 1996. Since then, under the auspices of the international Human Genome Organisations and with the acronym HGNC, we continue to strike a compromise between the convenience and simplicity required for the everyday use of human gene nomenclature and the need for adequate definition of the concepts involved. Numerical identifiers are satisfactory for computers, but when humans need to talk about a gene they prefer to use a name. Increasingly journals are requesting approved gene nomenclature before publication, although more standardisation in this respect would make a significant contribution to the annotation of the human genome (Povey et al. 1997; White et al. 1998). A recent analysis of networks of human genes from 10 million MedLine records illustrates the ingenuity currently required to extract information from the literature (Jenssen et al. 2001). The committee has grown from a single force (Dr Phyllis J. McAlpine) to the equivalent of five professional full-time staff, and operates through the Chair with key policy advice from an International Advisory Committee (IAC, http://www.gene.ucl.ac.uk/nomenclature/IAC.shtml). We also use a team of specialist advisors who provide support on specific gene family nomenclature issues (http://www.gene.ucl.ac.uk/nomenclature/advisors.html). Regular nomenclature workshops are held, frequently to coincide with the annual meeting of the American Society of Human Genetics (ASHG) and the HGM, to ensure that we are approving gene names in line with the needs of the scientific community. Guidelines for human gene nomenclature were last published in 1997 (White et al. 1977) and are also available online. New guidelines will be published in 2002 and a draft version can be inspected at http://www.gene.ucl.ac.uk/nomenclature/guidelines/draft _2001.html. For details of previous and future workshops see http://www.gene.ucl.ac.uk/nomenclature/workshops.html.

The DNA sequence and biological annotation of human chromosome 1

Abstract: The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Genew: the Human Gene Nomenclature Database

Abstract: Genew, the Human Gene Nomenclature Database, is the only resource that provides data for all human genes which have approved symbols. It is managed by the HUGO Gene Nomenclature Committee (HGNC) as a confidential database, containing over 16 000 records, 80% of which are represented on the Web by searchable text files. The data in Genew are highly curated by HGNC editors and gene records can be searched on the Web by symbol or name to directly retrieve information on gene symbol, gene name, cytogenetic location, OMIM number and PubMed ID. Data are integrated with other human gene databases, e.g. GDB, LocusLink and SWISS-PROT, and approved gene symbols are carefully co-ordinated with the Mouse Genome Database (MGD). Approved gene symbols are available for querying and browsing at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/ searchgenes.pl.

The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003

Abstract: The SWISS-PROT protein knowledgebase (http://www.expasy.org/sprot/ and http://www.ebi.ac.uk/swissprot/) connects amino acid sequences with the current knowledge in the Life Sciences. Each protein entry provides an interdisciplinary overview of relevant information by bringing together experimental results, computed features and sometimes even contradictory conclusions. Detailed expertise that goes beyond the scope of SWISS-PROT is made available via direct links to specialised databases. SWISS-PROT provides annotated entries for all species, but concentrates on the annotation of entries from human (the HPI project) and other model organisms to ensure the presence of high quality annotation for representative members of all protein families. Part of the annotation can be transferred to other family members, as is already done for microbes by the High-quality Automated and Manual Annotation of microbial Proteomes (HAMAP) project. Protein families and groups of proteins are regularly reviewed to keep up with current scientific findings. Complementarily, TrEMBL strives to comprise all protein sequences that are not yet represented in SWISS-PROT, by incorporating a perpetually increasing level of mostly automated annotation. Researchers are welcome to contribute their knowledge to the scientific community by submitting relevant findings to SWISS-PROT at swiss-prot@expasy.org.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

Integration of biological networks and gene expression data using Cytoscape

Abstract: Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.

TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes

Abstract: The TRANSFAC database on transcription factors, their binding sites, nucleotide distribution matrices and regulated genes as well as the complementing database TRANSCompel on composite elements have been further enhanced on various levels. A new web interface with different search options and integrated versions of Match and Patch provides increased functionality for TRANSFAC. The list of databases which are linked to the common GENE table of TRANSFAC and TRANSCompel has been extended by: Ensembl, UniGene, EntrezGene, HumanPSD and TRANSPRO. Standard gene names from HGNC, MGI and RGD, are included for human, mouse and rat genes, respectively. With the help of InterProScan, Pfam, SMART and PROSITE domains are assigned automatically to the protein sequences of the transcription factors. TRANSCompel contains now, in addition to the COMPEL table, a separate table for detailed information on the experimental EVIDENCE on which the composite elements are based. Finally, for TRANSFAC, in respect of data growth, in particular the gain of Drosophila transcription factor binding sites (by courtesy of the Drosophila DNase I footprint database) and of Arabidopsis factors (by courtesy of DATF, Database of Arabidopsis Transcription Factors) has to be stressed. The here described public releases, TRANSFAC 7.0 and TRANSCompel 7.0, are accessible under http://www.gene-regulation.com/pub/databases.html.